3-Amino-1-propanol → 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-N-(3-hydroxypropyl)-5-methyloxazole-4-carboxamide

HRID 595487Notes

Reaction equation

HRID 595487 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:16])=[C:11]([C:13]([OH:15])=O)[N:12]=2)=[C:4]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:3]=1.[NH2:21][CH2:22][CH2:23][CH2:24][OH:25].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:16])=[C:11]([C:13]([NH:21][CH2:22][CH2:23][CH2:24][OH:25])=[O:15])[N:12]=2)=[C:4]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:3]=1

Participants

6

Reactant 4

HCID 90863-Amino-1-propanolHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896897472-(6-Chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylic acid

Product 1

HCID 896896522-(6-chloro-4-(isopropylamino)pyridin-3-yl)-N-(3-hydroxypropyl)-5-methyloxazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylic acid (30a) (100 mg, 0.338 mmol) was dissolved in DMF (5 mL). 3-aminopropan-1-ol (1.691 mmol, 5 equiv.) and DIPEA (1.353 mmol, 4 equiv.) were added to the reaction mixture and stirred at room temperature. HATU (1.014 mmol, 3 equiv.) was added to the reaction mixture and stirred for 3 h. The reaction mixture was concentrated under reduced pressure to remove excess of DMF. The residue obtained was partitioned between water and EtOAc. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by flash column chromatography through silica gel and MeOH:CHCl3 as eluent to afford the title compound, 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-N-(3-hydroxypropyl)-5-methyloxazole-4-carboxamide (31).

Workup

  1. stirringstirred for 3 h
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto remove excess of DMF
  4. customThe residue obtained
  5. customwas partitioned between water and EtOAc
  6. customThe organic layer was separated
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material obtained
  11. customwas purified by flash column chromatography through silica gel and MeOH

Sources & evidence

ORD record
ord-d0d3081417024884bafb50773e6435dc
Source dataset
uspto-grants-2016_01
Patent number
US09242976B2

Reaction notes

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